Reading the different guidelines (USP / EP / ICH / Guidance of industry) about analytical methods' validation and impurities in new drug substances, it is still confusing for me what we have to do during HPLC method validation as concerns the LD / LQ / linearity and accuracy of impurities.

For the methods we have validated till now, we usually had isolated related substances, found the LD / LQ of them and demonstrated linearity and accuracy of all of them between their LQ and 120% of their specification limits. (Is this really needed or we are working "too much"?)

But what we can do when we have no available impurities? I mean some of the impurities are identified but we donīt have them purily isolated (only with 30-80% area). This means that we can not determine their LD and LQ, or can we? And the response factor of them?

Can anybody make this subject clear for me?

Hi Kati,

we treat impurities, which we have not (ie we are unable to do this) isolated or synthesized, like the active substance itself, ie we determine LD/LQ/linearity for the API and we use a diluted solution of the API as an external standard for the quantitation of the impurities.

Best regards,

Ulo